In many species, instinctive reactions to olfactory stimuli are mediated by specialized channels. Probing these representations offers an excellent opportunity to explore the first steps in complex behaviors. The question of specialized olfactory coding is particularly tractable in the Drosophila antennal lobe, a brain structure analogous to the vertebrate olfactory bulb. Major design principles within the two structures are conserved: odor molecules are sensed by olfactory receptor neurons, which in turn send information about odor stimuli to the olfactory bulb (in vertebrates), or the antennal lobe (in insects). All the receptor neurons that express the same olfactory receptor send information to the same discrete region (glomerulus) in the brain. What happens next-when olfactory information is processed by neural circuits in the brain-is still poorly understood. One difficulty is the complexity of olfactory space. Drosophila is a good model system for investigating this problem, given that the fly olfactory system is broadly similar to that of vertebrates, but much simpler, and given the range of genetic tools available in the fruit fly. This study examines how specialized olfactory information is processed by the circuitry of the antennal lobe. In particular, these experiments will dissect the odor-evoked electrophysiological response of first and second order olfactory neurons in the antennal lobe (olfactory receptor neurons, or ORNs and projection neurons, or PNs) and their contributions to olfactory-mediated behavior using specific genetic manipulations of sensory inputs targeting single glomeruli. In vivo extracellular and whole-cell patch-clamp recordings will be used to assess the responses of ORNs and PNs to olfactory stimulation of the fly's antennae. Specific Aim #1 tests the hypothesis that specialist ORNs are required for innate behavioral responses to their cognate ligand. Aim #2 tests the hypothesis that neurons directly post-synaptic to specialist ORNs are as narrowly tuned as their pre-synaptic ORN partner. Aim #3 tests the hypothesis that neurons directly post- synaptic to specialist ORNs are required for innate behavioral responses to the cognate ligand of their pre- synaptic partner ORNs. It is important to address these questions in Drosophila because of the unique advantages the fruit fly offers in investigating the circuit basis of innate behavior. This project should contribute substantially to our understanding of specialized olfactory processing and enhance our understanding of how organisms monitor their environment. Furthermore, research into insect olfaction should help us understand and prevent the spread of insect-born diseases. [unreadable] [unreadable] [unreadable]